Summary This application requests funding for a state-of-the-art shared mass spectrometer that will provide collaborative research for the Loma Linda University mass spectrometry facility. The LTQ-Orbitrap-XL-ETD mass spectrometer is manufactured by Thermo Fisher Scientific. The LTQ-Orbitrap-XL-ETD LC/MS/MS system provides understanding sensitivity, resolving power, accuracy of mass measurement, and wide dynamic range characteristics. It combines three different and complementary fragmentation techniques CID, HCD, and ETD with the proven benefits of Orbitrap technology for most comprehensive solution for complex PTM analysis, intelligent sequencing of peptides, top-down and middle-down analysis, and protein quantification via label-free or stable isotope labeling such as iTRAQ and TMT. As the cost of purchasing this mass spectrometer is $729,000, we request $499,999.23 from NIH shared instrumentation program and the School of Medicine of Loma Linda University will commit $229,000.77. This mass spectrometer will support 11 major NIH users in nine departments or centers at Loma Linda University and 2 major users from nearby institutes, Dr. Michael Grunstein at UCLA and Dr. Jian-Kang Zhu at UCR, who will collaborate with our facility to pursue their research in epigenetics. More than 30 investigators (major users and minor users), majority of whom holds NIH grants, will be benefited from this instrument. With acquisition of this instrument our major NIH users'research will be significantly advanced in the areas including identification of biomarkers in disease and cancer, neuron-injury and neonatal pain, understanding the mechanisms involved in DNA damage and repair, pathology of infectious disease, and histone modifications in epigenetic and cancer studies. PUBLIC HEALTH RELEVANCE: We request a LTQ-Orbitrap-XL-ETD mass spectrometer to meet the needs of our NIH sponsored users to advance their research in epigenetics, infectious disease, neuron injury, pain, hypoxia stress and human cancers, etc.